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Published on: June 14, 2020
Henipavirus-induced neuropathogenesis in mice.
Sarah J Edwards1, Brenton Rowe2, Tristan Reid2
1Commonwealth Scientific and Industrial Research Organisation (CSIRO), Australian Centre for Disease Preparedness (ACDP), 5 Portarlington Road, East Geelong, VIC, 3219, Australia; Department of Microbiology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC, 3800, Australia.
Hendra virus (HeV) can infect the mouse brain, but Nipah virus (NiV) cannot, despite both being deadly henipaviruses. Recombinant viruses confirmed HeV neuroinvasion, suggesting other factors limit NiV brain infection in mice.
Area of Science:
- Virology
- Neuroscience
- Pathogenesis
Background:
- Hendra virus (HeV) and Nipah virus (NiV) are henipaviruses causing fatal human encephalitis.
- Mouse models are crucial for studying henipavirus pathogenesis and neuroinvasion.
- Intranasal challenge with HeV can lead to neurological infection in mice, unlike NiV.
Purpose of the Study:
- To investigate the role of specific viral proteins in henipavirus neuroinvasion in mice.
- To compare the neuroinvasive potential of HeV and NiV in a mouse model.
Main Methods:
- Generation of recombinant HeV (rHeV) and NiV (rNiV) with swapped proteins.
- In vitro analysis of viral growth kinetics.
- Intranasal challenge of mice with wildtype and recombinant viruses.
- Detection of virus in brain tissue.
- In vitro infection of primary mouse neurons.
Main Results:
- Recombinant viruses exhibited similar in vitro growth kinetics to wildtype viruses.
- Infection outcomes in mice did not differ between wildtype and recombinant viruses.
- Virus was detected in the brain of 5/30 rHeV-challenged mice, but not in NiV-challenged mice.
- Primary mouse neurons were susceptible to both HeV and NiV infection in vitro.
Conclusions:
- Specific viral proteins do not appear to be the sole determinants of differential neuroinvasion between HeV and NiV in mice.
- Mouse neurons are permissive to both viruses in vitro.
- Other pathobiological factors likely contribute to the observed differences in NiV and HeV neuroinvasion in the mouse model.
